Targeting WNT signaling in the treatment of osteoporosis

Abstract

Osteoporosis is a widespread chronic disease characterized by low bone density, altered microstructure and bone fragility, leading to low impact fractures in affected individuals. The discovery of a few mutations that cause extremely rare human diseases has identified the WNT signaling pathway as a candidate for therapeutic intervention aimed at increasing bone mass and strength. In particular, inhibition of sclerostin, a WNT antagonist secreted by osteocytes, has proven in clinical trials to be a very efficient osteo-anabolic approach. One year of monthly administration of antibodies to sclerostin rapidly decreases bone resorption and increases bone formation and bone density at all sites, decreasing markedly fracture risk in treated patients. Their effect is however limited in time and cardiovascular adverse events have been reported in one clinical trial.